PF-06878031 合成路线的开发第 1 部分：选择性烷基化路线

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-04-19 DOI:10.1021/acs.oprd.4c00053

Oriana Brea, Julia Buck, Nessa Carson, Andrew M. Derrick, Steven J. Fussell, Adam E. S. Gymer, Michael Hawksworth, Adam W. Hopkins, Heather Ingram, Rebecca A. Johnson, Daniel A. Laity, Jinu S. Mathew, Ian B. Moses, James Rellegue, Emily K. Rose, Steven J. R. Twiddle* and Adam West,

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引用次数: 0

摘要

目标化合物 PF-06878031 是我们实验室正在开发的一系列口服后期胰高血糖素样肽-1 受体激动剂 (GLP-1-RA) 的关键结构片段，用于治疗 2 型糖尿病 (T2DM) 和减肥。本文介绍了选择性烷基化路线的确定和工艺的开发，该工艺能够提供多公斤量的 PF-06878031。该工艺的开发提高了安全性，增加了产量，减少了步骤数，降低了 PMI。新工艺已在多个工厂推广，可生产 1.5 公吨高纯度 PF-06878031。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Development of the Synthetic Route to PF-06878031 Part 1: Selective Alkylation Route

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Development of the Synthetic Route to PF-06878031 Part 1: Selective Alkylation Route

The target compound PF-06878031 is a key structural fragment of a range of oral late-stage glucagon-like peptide-1 receptor agonists (GLP-1-RA) under development in our laboratories for the indications of type-2 diabetes mellitus (T2DM) and weight loss. This article describes the identification of a selective alkylation route and development of a process, capable of delivering multikilo quantities of PF-06878031. Process development afforded improved safety, increased yield, reduced step count, and lowered PMI. The new process has been scaled up at multiple facilities to generate >1.5MT of high purity PF-06878031.

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.

PF-06878031 合成路线的开发 第 1 部分：选择性烷基化路线

摘要

PF-06878031 合成路线的开发第 1 部分：选择性烷基化路线